Device and method for making a segmented tubular capsule containing a biologically active medium

ABSTRACT

Method of manufacturing a tubular capsule comprising fiber ( 11 ) having a wall delimiting internal compartments ( 11   b ) that are isolated from one another, the wall being made from a solution of at least one polymer and the compartments ( 11   b ) being full of a biologically active medium, the method comprising the steps of: 
     coextruding the solution of at least one polymer and the biologically active medium by simultaneously injecting the polymer solution and the biologically active medium through a die ( 7 ) of determined dimensions; 
     interrupting the injection of the biologically active medium at determined points in time to form in the fiber ( 11 ) successive compartments ( 11   b ) full of the biologically active medium and separated by a solid partition section ( 11   a ) consisting only of the polymer solution; 
     immersing the fiber ( 11 ) in a coagulation liquid as it leaves the die ( 7 ) so as to initiate early coagulation of the polymer solution around the outside of the fiber ( 11 ); and 
     simultaneously driving the fiber ( 11 ) through the coagulation liquid along a determined path.

BACKGROUND OF THE INVENTION

Field of the Invention

The present invention relates to the manufacture of a capsule containinga biologically active medium, intended to be implanted in a livingorganism for therapeutic purposes. In the conventional way, a capsule ofthis type consists of a core comprising a biologically active medium,which is surrounded by a semipermeable casing. The role of the casing isto isolate the biologically active medium from the tissues of thereceiving organism while at the same time allowing substances via whichthe implanted capsule fulfils its functions to pass through the casing.By way of example, when the biologically active medium is a suspensionof cells, the semipermeable casing must act as a barrier to immunereactions, must allow nutrients to diffuse towards the core of thecapsule and must allow the substance of therapeutic benefit secreted bythe cells (insulin, for example, when the cells are islets ofLangerhans) to diffuse towards the organism.

From the point of view of the efficiency of the exchanges across themembrane, it would seem that spherical capsules are preferred overtubular capsules. However, spherical capsules have the drawback of beingdifficult to locate when implanted, which means that at the present timeit would not be possible to implant them in a human body from which theimplants have always to be able to be extracted for reasons ofbiological safety.

Recent research has therefore been mainly centred on manufacturingtubular capsules, which allow the shaping of implants that are longenough that they can be easily found. In particular, it has beendiscovered that it is preferable to segment the tubular capsules, thatis to say to form therein compartments which are isolated from oneanother, so that if part of an implanted capsule is damaged, it ispossible to separate it from the implant and extract it from thereceiving organism.

U.S. Pat. No. 5,158,881 describes a method of manufacturing a segmentedtubular capsule, comprising the steps of:

coextruding a polymer solution intended to form the casing of thecapsule and a biologically active medium by simultaneously injecting thepolymer solution and the biologically active medium through a die, and

interrupting the injection of the biologically active medium atdetermined points in time to form in the fibre successive compartmentsfull of the biologically active medium and separated by a solidpartition section consisting only of the polymer solution.

This method does not yield the desired results when the polymer solutionis liquid because, when the injection of biologically active medium isinterrupted, a drop of polymer solution forms under the die, deforms andbreaks under the effect of the weight of the fibre already formed whichhangs from the die.

The object of the invention is to improve the above-described method insuch a way as to make it possible to manufacture a segmented tubularcapsule from a liquid polymer solution. Another object of the inventionis to shape a tubular capsule into a shape that can be directlyimplanted.

BRIEF SUMMARY OF A FEW ASPECTS OF THE INVENTION

To achieve this objective, there is provided, according to theinvention, a method of manufacturing a tubular capsule comprising a walldelimiting internal compartments that are isolated from one another, thewall being made from a solution of at least one polymer and thecompartments being full of a biologically active medium, the methodcomprising:

coextruding the solution of at least one polymer and the biologicallyactive medium by simultaneously injecting the polymer solution and thebiologically active medium through a die of determined dimensions,

interrupting the injection of the biologically active medium atdetermined points in time to form in the fibre successive compartmentsfull of the biologically active medium and separated by a consistingpartition section consisting made of of the polymer solution,

causing partial early solidification of the fibre as it leaves the dieto a sufficient extent to prevent the fibre from breaking at thepartition sections.

As a preference, partial early solidification of the fibre may include:

immersing the fibre in a coagulation liquid as it leaves the die so asto initiate early coagulation of the polymer solution around the outsideof the fibre; and

simultaneously driving the fibre through the coagulation liquid along adetermined path.

This method may have at least two major benefits. On the one hand, itmakes it possible to envisage industrial-scale or semi-industrial-scaleimplant production. On the other hand, bringing the fibre leaving thedie into early contact with the coagulation liquid allows some of thesolvent used to prepare the polymer solution to be extracted, which issomething that is particularly desirable when the biologically activemedium contains living cells which may be adversely affected by thesolvents commonly used.

According to one feature of the invention, the method further comprises,at the same time as partially solidifying the fibre, exerting adetermined tensile force on the fibre so as to give it at least onegeometric characteristic that is independent of the dimensions of thedie.

By virtue of this arrangement, it is possible to extrude low viscositypolymer solutions.

According to another feature of the invention, the method furthermorecomprises giving the fibre a permanent shape. For example, the fibre iswound onto a cylindrical mandrel in such a way as to adopt the shape ofa spiral, the pitch of which is chosen to be such that each section offibre comprising a whole number of compartments corresponding to animplantable capsule occupies a determined length of mandrel.

By virtue of this arrangement, the dimensions of the implantable capsulecan be adjusted to suit the size of the receiving organism. It has beenfound that the spiral-wound shape was particularly well-suited toimplants in that it gave them mechanical robustness, in that it madethem easier to handle and in that it made them easier to implant in anorganism.

Another subject of the invention is a device for manufacturing a tubularfibre comprising a wall delimiting internal compartments isolated fromone another and full of a biologically active medium, comprising:

extrusion means of determined dimensions for coextruding a solution ofat least one polymer and the biologically active medium in such a way asto obtain a tubular fibre having a wall made from the polymer solutionand filled with the biologically active medium;

means for supplying the extrusion means with the polymer solution andwith the biologically active medium;

means for controlling the simultaneous supply of the extrusion meanswith polymer solution and with biologically active medium and forinterrupting the supply of biologically active medium at determinedpoints in time so as to form within the fibre successive compartmentsfilled with the biologically active medium and separated by a solidpartition section consisting only of the polymer solution;

the device being characterized in that it comprises:

means for causing partial solidification of the fibre as it leaves theextrusion means, this solidification being enough to prevent the fibrefrom breaking at the partition sections.

As a preference, the solidification means comprise:

a bath for a coagulation liquid placed under the extrusion means at achosen distance so that a fibre flowing out from the die at a givenoutput rate begins to coagulate early from the outside and does notbreak; and

means for driving the fibre through the coagulation liquid along adetermined path.

According to one feature of the invention, the device further comprisesmeans for exerting a determined tensile force on the fibre so as to giveit at least one geometric characteristic that is independent of thedimensions of the extrusion means.

In one embodiment of the invention, the driving means and the means forexerting a tensile force comprise a tube passing through the bottom ofthe coagulation bath and having an upper end inside the bath and a lowerend outside the bath, this tube being arranged substantially verticallyand its upper end lying below the surface of the coagulation liquid whenthe bath is filled to a determined operating level.

This embodiment is particularly advantageous because it allows severalfunctions to be fulfilled using very simple and inexpensive technicalmeans. Furthermore, it is easy to regulate and allows very low tensileforces to be exerted on the fibre, if appropriate.

According to one feature of the invention, the device further comprisesmeans for giving the fibre a determined shape. For example, the shapechosen is a spiral and the means for giving the fibre this shapecomprise:

a mandrel made up of disassemble portions;

means for rotating the mandrel;

a guiding device for moving the fibre with a back and forth movementparallel to the mandrel.

Advantageously, in operation, the rotational speed of the mandrel andthe speed of the back and forth movement of the guiding device arechosen so that the portion of fibre wound in a spiral onto the length ofa portion of mandrel corresponds approximately to a determined wholenumber of internal compartments of the fibre.

By virtue of this arrangement, it is possible to limit the handling ofthe shaped fibre as far as possible: all that is required is to ensurethat the length of fibre needed to form an implantable capsule is woundonto each mandrel portion. When the fibre is wound along the entirelength of the mandrel, the fibre is cut at the junction between twocontiguous mandrel portions and the mandrel portions are separated andcan act as supports for the implantable capsules during despatch andstorage.

Other features and advantages of the invention will become clear fromreading the description which follows. Reference will be made to theappended drawings, in which:

BRIEF DESCRIPTION OF SEVERAL VIEWS OF THE DRAWINGS

FIG. 1 depicts, diagrammatically, a plan view of a first part of adevice for manufacturing a segmented tubular capsule according to theinvention;

FIG. 2 depicts, diagrammatically, the extrusion and solidification meansof the device according to the invention;

FIG. 3 depicts, diagrammatically, a view from above of a second part ofa device for the manufacture of a segmented tubular capsule according tothe invention.

DESCRIPTION OF PREFERRED EMBODIMENTS

The device of FIG. 1 comprises a first reservoir 1 for containing abiologically active medium, in liquid form, such as a suspension ofcells. This reservoir is placed in a temperature control chamberallowing the contents of the reservoir 1 to be kept at constanttemperature. There is a second reservoir 2 for containing a polymersolution. The two reservoirs 1 and 2 are hermetically sealed and areconnected by pipes 3, 4 to a gas-pressure regulating system 5 thatallows a constant pressure to be set and maintained in each reservoir.The pressure-regulating system 5 is connected to a control unit 6 whichcontrols the pressure regulation in each reservoir on the basis of datumvalues communicated beforehand to the control unit 6 by an operator,using a keyboard (not depicted).

The reservoirs 1 and 2 and the gas-pressure regulating system 5constitute the means of supplying extrusion means 7 which have twoconcentric tubular nozzles, the inner nozzle 71 being connected by pipe8 to the reservoir 1, and the outer nozzle 72 being connected by a pipe9 to the reservoir 3.

In accordance with the invention, means 10 for causing earlysolidification of a tubular fibre 11 exiting the extrusion means arearranged vertically in line with the concentric nozzles 71, 72. As canbe seen in greater detail in FIG. 2, these early solidification meanscomprise a coagulation bath 101 with a bottom pierced by a hole for thepassage of a tube 102, flared at its top, the central longitudinal axisof which is essentially aligned with the central longitudinal axis ofthe nozzles 71, 72. As a result Of this layout, the tube 102 has a topend inside the Coagulation bath 101 and a bottom end outside this bath.The Tube 102 is mounted so that it can be slid in a vertical direction,so that the height of water between the top end of the tube 102 and areference water level in the coagulation bath 102 can be set accurately.

The choice of length of the tube 102, of its inside diameter, and of theheight of water between the reference level and the top end of the tubeallows the action exerted on the fibre, simple driving or pulling, to beregulated accurately. For the same head of water, and for a tube of thesame inside diameter, the longer the tube, the lower the tension. Forthe same head of water, and for a tube of the same length, the smallerthe inside diameter of the tube, the lower the tension. For the samelength of tube and the same inside diameter, the lower the head ofwater, the lower the tension.

In the embodiment depicted, the reference water level with respect towhich the position of the tube 102 in the bath is regulated, is definedby filling the bath 101 to the very top. In order constantly to maintainthe reference level and permanently to renew the coagulation liquid inthe bath 101, the bath 101 is placed in an overflow tank 103 which hasan overflow orifice 104. The coagulation bath 10 is connected by a pipe12 to a source 13 of coagulation liquid which, during operation,continuously feeds the coagulation bath 101.

A second coagulation bath 14 is arranged vertically in line with thetube 102 to receive the fibre 11 and complete coagulation. The distancebetween the bottom end of the tube 102 and the level of liquid in thesecond coagulation bath 14 is set according to the desired tension onthe fibre as it leaves the tube 102. The greater this distance, thegreater the tension, which is caused by gravity. Incidentally, thesecond coagulation bath 14 is used to collect the liquid from theoverflow tank 103 of the first coagulation bath 101. The secondcoagulation bath 14 is itself also connected to the source 13 ofcoagulation liquid and is equipped with an overflow pipe 15 allowing itscontents to be continuously renewed.

The device comprises guide members 16, 17 for guiding the fibre out ofthe second coagulation bath 14 towards a rotary cylinder 18 intended forthe temporary storage of the coagulated fibre. The cylinder 18 isarranged in a washing bath 19.

The temperature of the coagulation liquid in the baths 101 and 14, justlike the temperature of the washing liquid in the bath 19 may be set toany datum value by virtue of temperature-regulating means (notdepicted).

In accordance with the invention, the device also comprises means ofshaping the segmented tubular fibre. It has been seen that with certainpolymer solutions if, during a determined period of time after the fibrehas been removed from the coagulation bath, the fibre is subjected tomechanical deformation over a given time and at a given temperature,this deformation becomes permanent. In the embodiment depicted in FIG.3, the shaping means comprise a cylindrical mandrel 20 consisting ofportions 21 that fit together. This mandrel is mounted removably on astand 22 so that it can be partially immersed in a second washing bath25. One of its ends is coupled to a rotating motor 23 and its other endis supported by a bearing 24 and is free to rotate. The stand 22 furthercomprises support means (bearings 26) to receive the storage cylinder18, so that the latter can rotate about its longitudinal axis and bearranged parallel to the mandrel 20. Between the storage cylinder 18 andthe mandrel 20, there are various mechanical components secured to thestand 22 to allow part of the fibre wound on the cylinder 18 to betransferred onto the mandrel 20. These mechanical componentscomprise:—two guides 26, 27 allowing the fibre 11 to be keptperpendicular to the cylinder 18 and to the mandrel 20 over part of itslength;—a tensioner 28 exerting a vertical thrust on the fibre 11between the two guides 26, 27;—a guiding device comprising a rail 29parallel to the mandrel 20 and a carriage 30 that can move along therail 29 in a back and forth movement. The moving carriage is equippedwith a guide 31 for the fibre 11.

The device just described operates as follows. The entire device isplaced in a laminar-flow hood and all the liquids used (coagulationliquid, washing liquid) are sterile. The content of the coagulationbaths 101, 14 and washing bath 19 are kept at constant temperature. Thereservoirs 1, 2 are filled, one of them with polymer solution, and theother with a suspension of cells to be encapsulated. Thetemperature-regulating chamber is regulated to keep the suspension ofcells at an appropriate temperature. The various baths 101, 14, 19 arefilled. The value of the gas pressure for each of the reservoirs 1, 2 iscommunicated to the control unit 6. It is these values which, inparticular, determine the rate at which the tubular fibre 11 flows outof the die 7. When the device has been started up, the control unit 6controls the gas-pressure regulating system 5 in such a way that thesupply of suspension of cells to the die 7 is interrupted at regularmoments in time. The fibre which leaves the die is therefore a solid rod11 a, consisting only of polymer solution. According to the invention,to prevent the fibre 11 from breaking at this solid rod 11 a, which is adrop of liquid, early solidification of the fibre is brought about byimmersing it, a short distance from its exit from the die 7, in acoagulation liquid while driving it vertically downwards using theimmersed tube 102. It has been found that when there is no drive, thefibre, experiencing upthrust in the coagulation liquid, deformslongitudinally into zigzags and exhibits a very uneven cross section,which makes it unusable as an implant. As mentioned above, it is alsopossible to set the height of the tube 102 in the bath 101 in such a wayas to create a tensile force on the fibre 11 that allows the dimensionsof the fibre (outside diameter, wall thickness) to be regulatedindependently of the dimensions of the nozzles 71, 72 of the die 7. Assoon as the fibre 11 enters the coagulation liquid, solvent/nonsolventexchange (which defines coagulation) occurs from the outside of thefibre and limits the undesirable effects of purely internal coagulationwhich begins as soon as the suspension of cells comes into contact withthe polymer solution. In other words, the amount of solvent (which issomewhat toxic to the cells) which is extracted from the fibre from theoutside represents so much less solvent liable to migrate into thesuspension of cells during the process of coagulation from the inside.

The fibre 11 which emerges from the tube 102 is received in the secondcoagulation bath 14 where it solidifies enough that it can be handled.Note that the coagulation liquid in the baths 101 and 14 is permanentlyrenewed in order to eliminate the solvent. The fibre is then washed andwound onto the storage cylinder 18 to form a single spiral starting andfinishing respectively at each end of the cylinder.

To shape the fibre, a mandrel 20 is mounted on the rig 22. One end ofthe fibre wound onto the cylinder 18 is passed through the guides 26, 27and then into the guide 31 of the carriage 30 of the guiding device andis attached to one end of the mandrel 20. The length of the disassembleportions 21 of the mandrel 20, just like their diameter, are designedfor the definitive storage and shaping of implantable capsulescomprising a determined number of compartments 11 b. The speed of themotor 23 that rotates the mandrel 20, and the linear speed of thecarriage 30 of the guiding device are chosen to be such that a sectionof fibre comprising a whole number of compartments 11 b is wound ontoeach portion 21 of the mandrel 20, and that there is a section of fibreformed of solid rod 11 a at each end of each mandrel portion 21. Therotational speed of the mandrel 20 is increased each time the fibrereaches the end of each mandrel portion 21 so that the formed turns ofsolid rod are further apart than the rest of the turns and so thatseparating two adjacent implantable capsules is easier. A single spiralis formed on the mandrel 20, starting and ending respectively at eachend of the mandrel. The implantable capsules can then be separated fromone another while at the same time keeping them, for storage andtransport, attached to the mandrel portion on which they have beenrespectively spiral-wound.

EXAMPLE 1

The reservoir 2 was filled with a polymer solution containing 8% byweight of an acrylonitrile-sodium methallylsulphonate copolymer (knownby the trade name AN69), 6% by weight of physiological saline (solutionof sodium chloride in water, at a concentration of 9 g/l) and 86% ofdimethyl sulphoxide (DMSO). The contents of the reservoir were atambient temperature (about 25° C.).

The reservoir 1 was filled with a suspension of islets of Langerhans ata concentration of 10 000 EI/ml (EI=equivalent islet, corresponding to atheoretical islet 150 μm in diameter) in agarose (Sigma Type IA-A0169-batch No.-54 H 0530) at 0.5% (weight/volume) resulting from mixinga suspension of islets in HAM'S F12 (Sigma N8641-batch No.-123 H 2322)and a 0.65% (weight/volume) solution of agarose in physiological saline.The contents of the reservoir 1 were kept at 40.5° C.

The coagulation baths 101 and 14 are filled with sterile physiologicalliquid which is permanently renewed. The die used, manufactured by thecompany SCP-France had the following dimensions: inside diameter of theouter nozzle 72=1570 μm; outside diameter of the inner nozzle 71=980 μm;inside diameter of the inner nozzle 71=860 μm.

The tube 102 of the means for bringing about early solidification of thefibre 11 was a glass tube with an inside diameter of 0.003 m and alength of 0.25 m. The position of the tube 102 with respect to thecoagulation bath 101 was adjusted such that the height of water betweenthe top end of the tube 102 and the reference level was 0.005 m. Thebottom end of the tube 102 was placed 0.05 m from the level of liquid inthe second coagulation bath 14.

The height of the die 7 above the coagulation bath 101 was regulatedsuch that the orifice of the die 7 was 0.002 m from the reference waterlevel.

The contents of the coagulation baths 101, 14 and washing bath 19 weremaintained at 25° C.

The datum values for the operating parameters communicated to thecontrol unit 6 were as follows: pressure in reservoir 1=atmosphericpressure+80 mmHg; pressure in reservoir 2=atmospheric pressure+100 mmHg;the time for which the injection of the suspension of cells through thedie 7 was interrupted was set at 0.40 seconds every 5.8 seconds.

Under these operating conditions, and with the hardware described above,there was obtained, after the start-up phase, a segmented tubular fibrewith an inside diameter of about 1050 μm, a wall about 150 μm thick, andinternal compartments about 0.6 m long. An implantable capsulecontaining about 30 000 EI, formed with this tubular fibre, was about3.2 m long (namely five compartments).

The fibre 11 was transferred from the cylinder 18 onto the mandrel 20one hour after the fibre was manufactured. After 18 hours at 37° C., thefibre detached from the mandrel 20 retained a spiral shape.

EXAMPLE 2

Reservoir 2 was filled with a polymer solution containing 16% by weightof an acrylonitrile-vinyl acetate copolymer and 84% by weight ofdimethylformamide (DMF). The contents of the reservoir 2 were at ambienttemperature (about 25° C.).

The reservoir 1 was filled with a solution of Blue Dextran (Sigma-D5751)at a concentration of 1% by weight in physiological saline. The contentsof the reservoir 1 were at ambient temperature.

The coagulation baths 101 and 14 were filled with sterile physiologicalliquid which was permanently renewed. The die used was the same as theone used in Example 1.

The tube 102 of the means for bringing about solidification of the fibre11 was a glass tube with an inside diameter of 0.003 m and a length of0.10 m. The position of the tube 102 with respect to the coagulationbath 101 was adjusted such that the height of water between the top endof the tube 102 and the reference level was 0.005 m. The bottom end ofthe tube 102 was placed 0.05 m from the level of liquid in the secondcoagulation bath 14.

The height of the die 7 above the coagulation bath 101 was regulatedsuch that the orifice of the die 7 was 0.002 m from the reference waterlevel.

The contents of the coagulation baths 101, 14 and washing bath 19 weremaintained at 25° C.

The datum values for the operating parameters communicated to thecontrol unit 6 were as follows: pressure in reservoir 1=atmosphericpressure+39 mmHg; pressure in reservoir 2=atmospheric pressure+360 mmHg;the time for which the injection of the solution of Blue Dextran throughthe die 7 was interrupted was set at 0.75 seconds every second.

Under these operating conditions, and with the hardware described above,there was obtained, after the start-up phase, a segmented tubular fibrewith an inside diameter of about 980 μm, a wall about 180 μm thick, andinternal compartments about 0.05 m long.

The fibre 11 was transferred from the cylinder 18 onto the mandrel 20one hour after the fibre was manufactured. After 24 hours at ambienttemperature, the fibre detached from the mandrel 20 retained a spiralshape.

EXAMPLE 3

The reservoir 2 was filled with a polymer solution containing 15% byweight of polyethersulphone (PES), 5% by weight of polyethylene oxidewith a molecular mass=10 kdaltons (Sigma-P6667), and 80% by weight ofN-methylpyrrolidone (NMP). The contents of the reservoir 2 were atambient temperature (about 25° C.).

The reservoir 1 was filled with a solution of Blue Dextran (Sigma-D5751)at a concentration of 1% by weight in physiological saline. The contentsof the reservoir were at ambient temperature.

The coagulation baths 101 and 14 were filled with sterile physiologicalliquid which was permanently renewed. The die used was identical to theone used in Example 1.

The tube 102 of the means for bringing about solidification of the fibre11 was a glass tube with an inside diameter of 0.003 m and a length of0.10 m. The position of the tube 102 with respect to the coagulationbath 101 was adjusted such that the height of water between the top endof the tube 102 and the reference level was 0.005 m. The bottom end ofthe tube 102 was placed 0.05 m from the level of liquid in the secondcoagulation bath 14.

The height of the die 7 above the coagulation bath 101 was regulatedsuch that the orifice of the die 7 was 0.002 m from the reference waterlevel.

The contents of the coagulation baths 101, 14 and washing bath 19 weremaintained at 25° C.

The datum values for the operating parameters communicated to thecontrol unit 6 were as follows: pressure in reservoir 1=atmosphericpressure+50 mmHg; pressure in reservoir 2=atmospheric pressure+110 mmHg;the time for which the injection of the solution of Blue Dextran throughthe die 7 was interrupted was set, during a first test, at 0.35 secondsevery 1.25 seconds, then during a second test at 0.32 seconds every 0.55seconds.

Under these operating conditions, and with the hardware described above,there was obtained, after the start-up phase, a segmented tubular fibrewith an inside diameter of about 900 μm, a wall about 100 μm thick, andinternal compartments about 0.08 m long during the first test, and 0.03m long during the second test.

The fibre 11 was transferred from the cylinder 18 onto the mandrel 20one hour after the fibre was manufactured. After 24 hours at ambienttemperature, the fibre detached from the mandrel 20 retained a spiralshape.

The invention is not restricted to the embodiment just described and canbe varied.

What is claimed is:
 1. Method of manufacturing a tubular capsuleincluding fibre, the capsule having a wall delimiting internalcompartments isolated from one another, the wall being made from asolution of at least one polymer, and at least one of the compartmentscontaining a biologically active medium, the method comprising:coextruding the solution of at least one polymer and the biologicallyactive medium by simultaneously injecting the polymer solution and thebiologically active medium through a die of determined dimensions;interrupting the injection of the biologically active medium atdetermined points in time to form in the fibre successive compartmentscontaining the biologically active medium and separated by a partitionsection made from the polymer solution; and causing partial earlysolidification of the fibre as it leaves the die to a sufficient extentto prevent the fibre from breaking at the partition sections.
 2. Methodaccording to claim 1, wherein partial early solidification of the fibrecomprises: immersing the fibre in a coagulation liquid as it leaves thedie so as to initiate early coagulation of the polymer solution aroundthe outside of the fibre; and simultaneously driving the fibre throughthe coagulation liquid along a determined path.
 3. Method according toclaim 1 or 2, further comprising, at substantially the same time aspartially solidifying the fibre, exerting a determined tensile force onthe fibre so as to give it at least one geometric characteristic that isindependent of the dimensions of the die.
 4. Method according to one ofclaims 2 and 3, wherein the fibre is kept immersed in a coagulationliquid until it has solidified enough that it can be handled.
 5. Methodaccording to one of claims 2 to 4, further comprising washing the fibrewith a washing liquid after it has solidified in the coagulation liquid.6. Method according to one of claims 1 to 5, wherein the temperature ofthe coagulation liquid and/or the temperature of the washing liquid arekept at constant temperature.
 7. Method according to one of claims 1 to6, further comprising giving the fibre a permanent shape.
 8. Methodaccording to claim 7, wherein the fibre is given a permanent shape bywinding the fibre onto a cylindrical mandrel so as to give it the shapeof a spiral.
 9. Method according to claim 8, wherein the pitch of thespiral is chosen to be such that each portion of fibre comprising awhole number of compartments occupies a determined length of mandrel.10. Method according to one of claims 2 to 9, wherein the coagulationliquid is permanently renewed.
 11. Method according to one of claims 1to 10, wherein the solution of at least one polymer comprises anacrylonitrile-sodium methallylsulphonate copolymer, water and dimethyllsulphoxide.
 12. Method according to one of claims 1 to 11, wherein thebiologically active medium is a suspension of cells.
 13. Methodaccording to claim 1, wherein both compartments contain biologicallyactive material.